Showing papers on "Hypophysectomy published in 1981"

Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro.

Abstract: The direct effects of glucocorticoids on testicular LH receptor content and steroidogenesis were studied in vivo and in vitro. Immature hypophysectomized rats were treated with varying doses of dexamethasone, corticosterone, or a synthetic progestin, 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020). Some animals were also treated concomitantly with FSH to prevent the hypophysectomy-induced decrease in testis functions. At the end of 5 days of treatment, testicular LH/hCG receptor content was measured by [125I]hCG binding assay while steroidogenic responsiveness was measured by in vitro incubation of testes. Dexamethasone decreased testicular LH receptor in control and FSH-treated hypophysectomized rats in doses as low as 10 microgram/day, whereas corticosterone (10 microgram/day) decreased testicular LH receptor in the FSH-treated rats but had no effect in rats not treated with FSH. In contrast, R5020 had no effect on testicular LH receptor content. In vivo treatment of hypophysectomized rats with FSH increased both basal and hCG-stimulated production of androstanediol in vitro. In contrast, concomitant treatment with dexamethasone, but not R5020, decreased both basal and hCG-stimulated testicular androstanediol production. The direct effect of glucocorticoids on testicular steroidogenic potentials was also studied in primary culture of testicular cells obtained from adult hypophysectomized rats. Treatment of cultured testicular cells wtih hCG increased testosterone production. The addition of various natural and synthetic glucocorticoids, but not R5020, to hCG-treated cells decreased testosterone production in a dose- and time-related manner (triamcinolone greater than or equal to dexamethasone greater than cortisol greater than or equal to corticosterone). A 40% decrease in testosterone production was apparent at 6 h after addition of 10(-7) M dexamethasone to hCG-treated cells. These results demonstrate the direct inhibitory effect of glucocorticoids on testicular LH receptor content and steroidogenesis, suggesting the adrenal glucocorticoids may regulate testis functions.

Continuous infusion of growth hormone feminizes hepatic steroid metabolism in the rat.

Abstract: The metabolism of 4-[4-14C]androstene-3,17- dione was studied in the microsomal fraction of rat livers after continuous administration of human GH (hGH) in Alzet osmotic minipumps under varying conditions. hGH caused a complete feminization of hepatic steroid metabolism (i.e. increased the 5α- reductase and decreased the 6β- and 16α-hydroxylase activities) in normal male rats when infused at a rate of 5 μg/h for 7 days. Hypophysectomy and castration or adrenalectomy and thyroidectomy of male rats did not reduce the feminizing capacity of hGH, indicating that the adrenals and the thyroid gland are not involved in the mediation of the feminizing effect of hGH. The same dose (5 μg/h for 7 days) of hGH was also able to refeminize the liver steroid metabolism in hypophysectomized-ovariectomized female rats. The effect of the homologous hormones, rat PRL and rat GH on hepatic steroid metabolism was also investigated. Either hormone was infused at a rate of 10 μg/h for 7 days, a dose which was sufficient to incr...

Ovarian gonadotropin-releasing hormone (GnRH) receptors: characterization, distribution, and induction by GnRH.

Abstract: Gonadotropin-releasing hormone (GnRH) and its analogs have direct extrapituitary effects on the gonads to inhibit steroidogenesis. In the present study, the nondegradable GnRH analog [125I]D-Alaa-des-Gly10-GnRH ethylamide is shown to specifically bind to ovarian, testicular, and adrenal membrane preparations. The ovarian GnRH receptor has a binding affinity similar to that of the anterior pituitary receptor and is specific for GnRH and GnRH analogs. The GnRH-binding capacity of whole ovarian membrane preparations is 150 fm/mg protein, 3- to 4-fold lower than that of anterior pituitary membranes. The number or affinity of receptors prepared from whole ovarian tissue is not influenced by the time of day, stage of the estrous cycle, or hypophysectomy. However, the GnRH receptor concentration is higher in follicular (371 ± 43 fmol/mg) than luteal (162 ± 25 fmol/mg) membranes from cycling rats. Since GnRH injections increase the number of GnRH receptors in the pituitary, the effect of GnRH on ovarian GnRH bind...

Multihormonal regulation of the estrogen receptor in rat liver

Abstract: Hepatic estrogen receptors were measured in ovariectomized female rats using isoelectric focusing in polyacrylamide gel. Hypophysectomy or adrenalectomy reduced the receptor level to approximately 10% and 42%, respectively, of the control value. Treatment of hypophysectomized (Hx) rats with dexamethasone alone was without effect. When Hx rats were given a pituitary transplant under the kidney capsule in order to induce liver estrogen receptors, dexamethasone treatment more than doubled the inductive effect of the pituitary transplant. The administration of human GH (hGH) in osmotic minipumps to Hx rats led to an induction of hepatic estrogen receptor levels to 48% of the control value. When hGH infusion was combined with dexamethasone treatment, a complete restoration of the receptor level to that in control rats was seen. When administered in minipumps, ovine PRL (oPRL) and bovine GH (bGH) as well as a combination of oPRL and bGH led to an induction of estrogen receptors in Hx rat livers when dexamethaso...

Sites of Androgen and Estradiol Production in the Second Half of Pregnancy in the Rat

Abstract: To determine the sites of androgen and estradiol production in the second half of pregnancy, pregnant rats were hypophysectomized or hypophysectomized and hysterectomized on Day 12. After hypophysectomy, the luteal weight, the concentration of androgen and estradiol in corpora lutea, and serum androgen remained at control values on Days 14, 18, and 22. In contrast, by Day 14 the nonluteal tissue atrophied, its estradiol concentration decreased, and serum estradiol declined from 25 ± 1.0 in sham-treated animals to 21 ± 0.3 pg/mI. When the conceptuses were removed together with the pituitary by hypophysectomy and hysterectomy on Day 12, androgen and estradiol levels in the serum dropped to barely detectable levels. To determine whether the placentas secreted androgen or stimulated androgen secretion by other endocrine glands, adrenals, ovaries, and/or fetuses were removed from rats hypophysectomized on Day 12, and pregnancy was maintained with progesterone treatment. No decrease in androgen levels in the serum was observed. Serum androgen remained elevated in all groups in which the placentas remained in utero. When the placentas were removed, as in hypophysectomized-hysterectomized rats, serum androgen dropped dramatically. However, while androgen levels remained elevated, serum estradiol declined after either ovariectomy or fetectomy and a synergism was observed when ovariectomy and fetectomy were combined. These results indicate that the placentas are a source of androgen in the second half of pregnancy and that the ovaries and fetuses are a site of estradiol production.

Aminoglutethimide: Review of Pharmacology and Clinical Use

Abstract: Aminoglutethimide blocks several cytochrome P-450 mediated steroid hydroxylation steps, including those required for conversion of cholesterol to pregnenolone and for the aromatization of androgens to estrogens. Through these actions it blocks adrenal steroidogenesis and the production of estrogens in extraglandular tissues. Aminoglutethimide is indicated for treatment of certain patients with Cushing's syndrome and breast cancer. Other potential uses (prostate carcinoma, low renin hypertension, etc.) remain investigational. For treatment of Cushing's syndrome, aminoglutethimide is usually given alone or in combination with metyrapone. In women with breast carcinoma, replacement hydrocortisone must be administered with aminoglutethimide to prevent reflex ACTH hypersecretion from overcoming adrenal inhibition. Administration of aminoglutethimide to patients with Cushing's syndrome results in improvement in clinical status in 56% of cases. Results are most favorable in patients with adrenal tumors and patients with ectopic ACTH production. Aminoglutethimide and replacement glucocorticoid produce objective disease regression in 32% of unselected postmenopausal patients with metastatic breast carcinoma and in 52% of women whose tumors are estrogen receptor positive. Responses are similar in duration and frequency to those produced by surgical adrenalectomy and hypophysectomy and the antiestrogen, tamoxifen.

Thyroid hormones and muscle protein turnover. The effect of thyroid-hormone deficiency and replacement in thryoidectomized and hypophysectomized rats.

Abstract: We have investigated the effects of thyroidectomy, hypophysectomy and 3,3',5-tri-iodothyronine replacement on protein synthesis and degradation in skeletal muscle in vivo. Thyroidectomy resulted in a decrease in the rate of protein synthesis as a result of a loss of RNA. However, RNA activity, the rate of protein synthesis per unit of RNA, was not decreased. This was the case in both young growing rats and mature nongrowing rats. Tri-iodothyronine treatment of thyroidectomized rats increased protein synthesis by increasing RNA concentration without changes in RNA activity, and this occurred even when food intake was restricted to prevent any increase in growth. The rate of protein degradation was decreased by thyroidectomy and increased by tri-iodo-thyronine replacement in both animals fed ad libitum and food-restricted animals. Hypophysectomy decreased protein synthesis by decreasing both RNA concentration and activity. these changes were reversed by tri-iodothyronine treatment even in the presence of persistent marked hypoinsulinaemia. This indicates that tri-iodothyronine can activate athe translational phase of protein synthesis in muscle in the absence of significant quantities of insulin. However, tri-iodothyronine does not seem to be obligatory for the maintenance of normal RNA activity in muscle, since in the thyroidectomized rat, in which plasma insulin concentrations are normal, RNA activity is maintained. From a consideration of the magnitude of changes in RNA activity observed in these experiments, it would appear that alterations in rates of elongation as well as initiation are involved in the changes in RNA activity.

Effect of Hypophysectomy on Atresia of Rat Preovulatory Follicles

Abstract: Atresia of Craafian follicleswas induced by hypophysectomy on the morning of the day of proestrus. As early as 6 h after hypophysectomy, follicles showed a reduced ability to respond with ovulation to administration of hCC, and 12 h after hypophysectomy all the follicles failed to ovulate. At 24 h after hypophysectomy, the follicles exhibited morphological changes characteristic of early atresia followed by advanced atresia at 48 h after the operation. Steroidogenesis in vitro of follicles from hypophysectomized rats was compared with that of sham-operated controls. The mean ± SEM rate of accumulation (ng/follicle/24 h) of progesterone, testosterone, and estradiol17$3 was 5.1 ± 0.9, 6.3 ± 0.5,and 20.2 ± 3.7, respectively, in control follicles; 12 h after hypophysectomy progesterone accumulation was 22.7 ± 4.9, testosterone4.5 ± 0.4, and estradiol-1 7j1 11.7 ± 0.9; and 48 h after the operation accumulation was 59.3 ± 8.3, 1.0 ± 0.3, and 0.10 ± 0.02, respectively. Thus atretic follicles from hypophysectomized rats are characterized by increased progesterone and decreased androgen and estradiol-17�3 production. Addition of LH to the culture medium stimulated progesterone accumulation in follicles from rats up to 24 h after hypophysectomy but not 48 h after the operation. It appears, therefore, that follicles gradually lose their responsiveness to LH during the atretic process.

Hormonal Control of Growth in the Infant Rat

Abstract: To obtain information on pituitary control of growth in infant rats, we employed a hypophysectomy technique which can be used on 4- to 6-day-old pups with an 80% success rate. A 30–50% reduction in body weight gain and a 30–40% decrease in tail growth were observed in the pups after hypophysectomy. The following hormone replacement injections were administered from days 7–15: ovine GH (oGH) or PRL (oPRL), at 1 or 4 μg/g BW, alone and in combination; T4 (40 ng/g for 4 days then 8 ng/g for 4 days) alone or in combination with the low dose of oPRL and/or oGH; and rat pituitary homogenate at 10 and 100 jug wet weight/g BW. Neither dose of oPRL increased weight gain or tail growth significantly. The high dose of oGH restored body weight gain and tail growth to 95% and 80%, respectively, of that in the sham controls. The low dose of GH increased both parameters to 75% of the sham values. Responses to injections of PRL and GH combined were intermediate between those of the hormones alone. T4 alone had no effect ...

Endocrine regulation of rat serum cholinesterase activity.

Abstract: Enzymological and endocrine studies of rat serum cholinesterase (CHE) suggest that this enzyme is subject to a complex and specific form of regulation. Adult CHE activity levels are 3-fold higher in adult females than in males. Gonadectomy and/or hypophysectomy abolish these sex differences. Androgen and estrogen replacement to gonadectomized but not to hypophysectomized animals reverses this action. Adrenalectomy produces no significant changes in serum CHE levels in either male or female rats. An ecotpic pituitary plus the appropriate steroid cannot reverse the effect of hypophysectomy. The catalytic properties of CHE alter concurrently with isozyme changes and are reflected in the changes in the ratio of hydrolysis of the butyryl and acetyl substrates. Androgens and estrogens, acting through the hypothalamic-hypophyseal axis, appear to modulate the synthesis of specific CHE isozymes. (Endocrinology 108: 1737, 1981)

The Mechanism of the Action of Growth Hormone on Vitamin D Metabolism in the Rat

Abstract: GH has been shown to stimulate intestinal calcium absorption in rats and humans. We have investigated in rats whether GH might affect intestinal calcium absorption by stimulating the production of 1,25-dihydroxyvitamin D3 [1,25- (OH)2D3], the active metabolite of vitamin D3. The tissue distribution of [3H]1,25-(OH)2D3 8–40 h after iv injection of [3H]25-hydroxyvitamin D3 ([3H]25OHD3) was measured in sham controls, hypophysectomized, and GH-treated hypophysectomized rats. Since the plasma disappearance rate of iv [3H]1,25-(OH)2D3 was not significantly affected by hypophysectomy, the recovery of [3H]1,25-(OH)2D3 after [3H]25OHD3 administration was taken to be an indirect measure of renal 25- OHD3-l-hydroxylase. Hypophysectomy was found to reduce the recovery of [3H]1,25-(OH)2D3 from serum and intestinal mucosa by 70 ± 2% (range). A 6-day course of GH treatment of hypophysectomized rats restored the formation of 1,25-(OH)2D3 to normal, and a significant effect was noted within 2 days, before any increase in ...

Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer.

Abstract: Fluoxymesterone (Halotestin), 10 mg p.o. BID, was given to 33 women with Stage IV breast cancer who had previously been treated wih the antiestrogen tamoxifen (Nolvadex) and of whom 17 had also undergone hypophysectomy. Objective remissions were obtained in 13 patients (39%) with an average duration of 11+ months. Response rate to fluoxymesterone was similar in patients who had previously responded to tamoxifen and in those who had failed. Duration of response was longer in the former group (12+ vs. 8 months), but this difference was not statistically significant. Of 17 patients who had been previously treated with tamoxifen and hypophysectomy, seven obtained further remission from fluoxymesterone for an average duration of ten months. Two patients with remissions from fluoxymesterone had previously failed to respond both to antiestrogen therapy and to the removal of the pituitary gland. Androgens appear to be an effective sequential endocrine treatment of Stage IV breast cancer after tamoxifen and hypophysectomy. The mechanism by which androgens induce tumor regression in some patients is probably not an antiestrogenic effect or an indirect effect mediated through the pituitary gland, but perhaps a direct action at the tumor level.

Prolactin and contact sensitivity.

Abstract: Hypophysectomized (Hypo-X) rats did not develop contact dermatitis in response to dinitrochlorobenzene (DNCB). Syngeneic pituitary grafts placed under the kidney capsule or daily treatment with prolactin restored the DNCB-reactivity of Hypo-X animals. Combined treatment with other pituitary hormones was ineffective. Treatment of normal rats with a potent prolactin antagonist drug, bromocriptine, was as effective in inhibiting contact sensitivity as was hypophysectomy. These results indicate that contact sensitivity is a prolactin dependent reaction.

Hypophysectomy and Simultaneous Testosterone Replacement: Effects on Male Rat Reproductive Tract arid Epididymal Δ4-5α-Reductase and 3α-Hydroxysteroid Dehy dr o genase

Abstract: Rat epididymal ΔA4-5α-reductase and 3α-hydroxysteroid dehydrogenase activities are differentially controlled. We have shown previously that 3α-hydroxysteroid dehydrogenase activity can be regulated by circulating testosterone, whereas Δ4-5α-reductase activity is at least partially dependent on direct testicular secretions. The present experiment was designed to determine if a certain testicular cell type(s) (Leydig cells, condensed spermat id, or spermatozoa) is responsible for elaborating this required substance. A hypophysectomy-testosterone replacement model was used. Adult male Sprague-Dawley rats were either left intact as controls (Co) or were hypophysectomized and simultaneously treated with subcutaneous polydimethylsiloxane implants, which were empty capsules (HP-O) or testosterone-filled capsules measuring 1.0 cm (HP-1), 2.4 cm (HP-2), or 22.0 cm (HP-3). The animals were decapitated 4 weeks later. The weights of the sex accessory tissues (ventral prostate and seminal vesicles) and the serum testo...

In-vitro metabolism of 4-androstene-3,17-dione by hepatic microsomes from the rainbow trout (Salmo gairdnerii): Effects of hypophysectomy and oestradiol-17β

Abstract: The metabolism of 4-androstene-3,17-dione by liver microsomes from juvenile rainbow trout, Salmo gairdnerii, was studied in vitro. Hypophysectomy of the fish significantly increased mean hepatic 17-hydroxysteroid oxidoreductase activity when compared with that from sham-operated fish but none of the other enzyme activities investigated were affected. Administration of oestradiol-17 beta resulted in a significant decrease in mean hepatic 6 beta-hydroxylase activity and total cytochrome P-450 content but had no effect on the 16-hydroxylase or on the reductive metabolism of androstenedione. The effect of oestradiol-17 beta on hepatic 6 beta-hydroxylase activity was as pronounced after hypophysectomy as after sham-operation indicating that these effects of oestradiol-17 beta are mainly direct and independent of the pituitary gland. The results indicate that hypophysial hormone(s) as well as oestradiol-17 betal play a role in the regulation of hepatic steroid metabolism in trout.

Relative Importance of the Adenohypophyseal and Gonadal Sites of Inhibitory Action of LHRH Agonists

Abstract: Assessment of the role of endogenous LH release and direct gonadal action of LHRH agonists in the loss of gonadal LH receptors induced by treatment with gonadotropin-releasing peptides was first made by comparing the effect of single administration of 1 �g of ID-Ala’, des-Gly-NH2 ‘#{176} I LHRH ethylamide, ED-Ala’) LHRH-EA, 12 h before or immediately after hypophysectomy (HYPOX) on LH receptor levels measured 48 h after surgery in male and female adult rats. While administration of the LHRH agonist before HYPOX leads to a 50% loss of testicular LH receptors, only a 20% decrease is seen in HYPOX animals, thus suggesting a predominant role of endogenous LH release in the desensitization process in male animals. Treatment with increasing doses (1 to 100 ng/day) of another LHRH agonist, [D-Ser(TBU)’ I LHRH-EA, causes a 90% loss of testicular LH receptors in intact rats at the highest dose used (100 ng daily for 9 days) while the same treatment decreases LH receptors by only 35% in HYPOX animals. As measured by the steroidogenic response to 10 �g 0LH in vivo, while treatment of intact animals with [D-Ser(TBU)’ I LHRHEA leads to a marked blockage of the testicular steroidogenic pathway at the level of 17-hydroxylase and 17,20-desmolase activities with a corresponding increase of 5o-reductase activity, minimal or no signs of changes of enzymatic activity are seen after identical treatment in HYPOX animals. Chronic treatment (1 month) with the LHRH agonist in intact rats leads to degenerative changes of the seminiferous tubules, while no effect is observed in HYPOX animals, thus suggesting the essential role of the pituitary gland. Moreover, adrenalectomy does not influence the inhibitory effect of treatment with LHRH agonists on the loss of testicular LH receptors in HYPOX animals, thus eliminating the role of the adrenals in the action of LHRH agonists. Contrary to the results obtained in male animals, single administration of the LHRH agonist in female rats has similar inhibitory effects on ovarian gonadotropin receptors when administered either before or after hypophysectomy. Moreover, treatment with increasing doses of ED-Ser(TBU)’ I LHRH-EA leads to a similar inhibition of ovarian LH receptor levels in intact and HYPOX female animals. The present data show that LHRI-I agonist-induced endogenous LH release plays a predominant role in the desensitizing effect of treatment with LHRH agonists on testicular LH receptors and steroidogenesis as well as on inhibition of spermatogenesis; in the female, the direct gonadal effect, at least on LH and FSH receptors, appears to play a more important role than in male animals.

Luteotropic role of the decidual tissue in the rat: dependency on intraluteal estradiol.

Abstract: The decidual tissue (DT) of pregnant and pseudopregnant rats maintains progesterone secretion in the absence of PRL. However, the luteotropic activity of the decidua disappears in the absence of the pituitary or LH. Since the role of LH in the pregnant rat is mediated by estradiol, it was of interest to determine whether the luteotropic role of the DT is dependent upon intraluteal estradiol. Pseudopregnant rats, either hysterectomized or bearing DT, were hypophysectomized on day 9. Within 24 h, a precipitous reduction in serum progesterone was observed in the two groups. The intraluteal concentration of estradiol on day 12 also dropped after hypophysectomy from 4 ± 1 and 2.8 ± 0.5 pg/mg in DT-bearing and hysterectomized animals to 0.4 ± 0.3 and0.2 ± 0.1 pg/mg, respectively. Three days after hypophysectomy, the average weight of the decidualized uteri was 1.1 ± 0.3 g compared to 3.9 ± 0.3 g in intact controls. Insertion of a 1-cm testosterone (T1) capsule in DTbearing rats 24 h before hypophysectomy increa...

Selective hormonal control of myo-inositol biosynthesis in reproductive organs and liver of the male rat.

Abstract: myo-Inositol biosynthesis has been examined in hypophysectomized and thyroidectomized male rats. After hypophysectomy, inositol-1-phosphate synthase [1L-myo-inositol-1-phosphate lyase (isomerizing), EC 5.5.1.4] in the reproductive organs and liver decreased markedly. At the same time, testicular acid phosphatase [orthophosphoric-monoester, phosphohydrolase (acid optimum), EC 3.1.3.2] and beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) increased. Thyroidectomy caused a similar decrease in inositol-1-phosphate synthase in the liver but not in the reproductive organs. Follicle-stimulating in the liver but not in the reproductive organs. Follicle-stimulating hormone (follitropin) and luteinizing hormone (lutropin) restored the activity to at least normal levels in the testis, prostate, and seminal vesicle but not in the liver of hypophysectomized animals. Triiodothyronine and thyroxine stimulated liver synthase 30-fold in hypophysectomized animals. We conclude that inositol-1-phosphate synthase in the reproductive organs is under more or less direct control of the pituitary; in the liver, the control is mediated through the thyroid.

Hypothalamic Luteinizing Hormone (LH): Characteristics and Response to Hypophysectomy

Abstract: This study describes the finding of an immunoassayable and bioassayable luteinizing hormone (LH) in the rat hypothalamus. Validation of the immunoassay forLH inhypothalamicextractsis presented. Chromatographic patterns of hypothalamic LH were found to be identical with those of rat pituitary LH. Radioimmunoassay values of serial dilutions of hypothalamic extract paralleled dilution values of rat pituitary LH. Furthermore, such homogenates promoted release of testosterone from dispersed rat testis cells in vitro. This effect was largely abolished by prior incubation of homogenate with an antiserum to rat LH. Following removal of the anterior pituitary, LH levels in the hypothalamus persist but drop significantly, signifying that this particular brain-based LH is partially dependent on the presence of a functioning pars distalis. Immunoassayable LH measured in other areas of the rodent central nervous system did not change following hypophysectomy.

The hypothalamic–hypophyseal–gonadal regulation of hepatic glutathione S-transferases in the rat

Abstract: Hepatic glutathione S-transferase activities were determined with the substrates 1,2-dichloro-4-nitrobenzene and 1-chloro-2,4-dinitrobenzene. Sexual differentiation of glutathione S-transferase activities is not evident during the prepubertal period, but glutathione conjugation with 1,2-dichloro-4-nitrobenzene is 2-3-fold greater in adult males than in females. Glutathione conjugation with 1-chloro-2,4-dinitrobenzene is slightly higher in adult males than adult females. No change in activity was observed after postpubertal gonadectomy of males or females. Neonatal castration of males results in a significant decrease in glutathione conjugation with 1,2-dichloro-4-nitrobenzene. Hypophysectomy, or hypophysectomy followed by gonadectomy did result in significantly higher glutathione S-transferase activities in both sexes. These increases can be reversed by implanting an adult male or female pituitary or four prepubertal pituitaries under the kidney capsule. Postpubertal sexual differentiation of glutathione S-transferase activities is neither dependent on pituitary sexual differentiation nor pituitary maturation. Prolactin concentrations are inversely related to glutathione S-transferase activities in hypophysectomized rats with or without ectopic pituitaries. Somatotropin exogenously administered to hypophysectomized rats results in decreased glutathione S-transferase activities, whereas prolactin has no effect. Adult male rats treated neonatally with monosodium l-glutamate to induce arcuate nucleus lesions of the hypothalamus have decreased glutathione S-transferase activities towards 1,2-dichloro-4-nitrobenzene and decreased somatotropin concentrations. Our experiments suggests that sexual differentiation of hepatic glutathione S-transferase is a result of a hypothalamic inhibiting factor in the male (absent in the female). This postpubertally expressed inhibiting factor acts on the pituitary to prevent secretion of a pituitary inhibiting factor (autonomously secreted by the female), resulting in higher glutathione S-transferase activities in the adult male than the adult female.

Brain adrenocorticotrophin after adrenalectomy and sham-operation of rats.

Abstract: The influence of adrenalectomy on the level of immunoreactive 18-24 ACTH extracted from hypothalamus, hippocampus and pituitary gland of rats was investigated. Brain ACTH was further characterized by fractionation by gel-permeation chromatography. Porcine 1-39 ACTH was exposed to synaptic plasma membranes in vitro in order to evaluate the role of metabolic conversion in changes of brain ACTH content. Removal of the adrenals, when compared with sham-adrenalectomy, resulted in a transient depletion of ACTH content in the anterior pituitary gland and the hippocampus, but not in the hypothalamus and the neurointermediate lobe. However, sham-adrenalectomy caused a transient reduction in levels of ACTH when compared with levels before operation in all tissues studied. The effects of adrenalectomy on hippocampal ACTH content persisted in hypophysectomized rats. Treatment of adrenalectomized rats with corticosterone failed to restore the reduced ACTH content when it was administered in doses that completely suppressed the release of pituitary ACTH. Adrenal steroids, however, may exert a direct effect on the metabolism of ACTH in the brain as judged from the in-vitro studies with porcine 1-39 ACTH exposed to a synaptosomal plasma membrane fraction of hippocampal tissue. The present study suggests that control of brain ACTH occurs independently of the control of pituitary ACTH release.